Enzymatic analysis of the effect of naturally occurring Leu138Pro mutation identified in SHV -lactamase on hydrolysis of penicillin and ampicillin

Nabin Rayamajhi; Jeong Chan Joo; Seung Bin Cha; Subarna Pokherl; Min Kyung Shin; Young Je Yoo; Han Sang Yoo

doi:10.1186/1471-2180-11-29

Enzymatic analysis of the effect of naturally occurring Leu138Pro mutation identified in SHV -lactamase on hydrolysis of penicillin and ampicillin

Nabin Rayamajhi, Jeong Chan Joo, Seung Bin Cha, Subarna Pokherl, Min Kyung Shin, Young Je Yoo, Han Sang Yoo

Department of Biotechnology

Seoul National University

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

Abstract

Background: The aim of this study was to analyze the significance of leucine to proline substitution at position 138(Leu138Pro) on the hydrolysis of penicillin and ampicillin that we identified in the bla_SHVgene of clinical Escherichia coli swine isolate. Results: Kinetic analysis of the mutant proteins showed that K_mvalue of the purified L138P mutant was comparatively higher than SHV-1, SHV-33 and SHV-33(L138P) enzyme for penicillin and ampicillin. Docking simulation of the SHV-1 and SHV-(L138P) enzymes also confirmed that β-lactamases preferred penicillin to ampicillin and the SHV-1 had a higher binding affinity for antibiotics compared to the SHV-(L138P) and other mutants. Conclusions: Our result demonstrated that L138P has a reduced role in penicillin and ampicillin hydrolyzing properties of SHV β-lactamases. These naturally occurring mutations rendering reduced function of the existing protein could trigger the emergence or acquisition of more effective alternative mechanisms for -lactam hydrolysis.

Original language	English
Article number	29
Journal	BMC Microbiology
Volume	11
DOIs	https://doi.org/10.1186/1471-2180-11-29
State	Published - 2011

Bibliographical note

Funding Information:
This work was supported by a Korea Research Foundation Grant funded by the Korean Research Foundation (KRF-2006-21-E00011, KRF-2006-005-J502901), a BK-21 grant, and a Bio-green 21 grant (20070401-034-009-007-01-00), RDA and the Research Institute for Veterinary Science, Seoul National University, Korea.

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@article{7de5d0437b0e4aa388ce9886c715dc93,

title = "Enzymatic analysis of the effect of naturally occurring Leu138Pro mutation identified in SHV -lactamase on hydrolysis of penicillin and ampicillin",

abstract = "Background: The aim of this study was to analyze the significance of leucine to proline substitution at position 138(Leu138Pro) on the hydrolysis of penicillin and ampicillin that we identified in the blaSHVgene of clinical Escherichia coli swine isolate. Results: Kinetic analysis of the mutant proteins showed that Kmvalue of the purified L138P mutant was comparatively higher than SHV-1, SHV-33 and SHV-33(L138P) enzyme for penicillin and ampicillin. Docking simulation of the SHV-1 and SHV-(L138P) enzymes also confirmed that β-lactamases preferred penicillin to ampicillin and the SHV-1 had a higher binding affinity for antibiotics compared to the SHV-(L138P) and other mutants. Conclusions: Our result demonstrated that L138P has a reduced role in penicillin and ampicillin hydrolyzing properties of SHV β-lactamases. These naturally occurring mutations rendering reduced function of the existing protein could trigger the emergence or acquisition of more effective alternative mechanisms for -lactam hydrolysis.",

author = "Nabin Rayamajhi and Joo, \{Jeong Chan\} and Cha, \{Seung Bin\} and Subarna Pokherl and Shin, \{Min Kyung\} and Yoo, \{Young Je\} and Yoo, \{Han Sang\}",

note = "Funding Information: This work was supported by a Korea Research Foundation Grant funded by the Korean Research Foundation (KRF-2006-21-E00011, KRF-2006-005-J502901), a BK-21 grant, and a Bio-green 21 grant (20070401-034-009-007-01-00), RDA and the Research Institute for Veterinary Science, Seoul National University, Korea.",

year = "2011",

doi = "10.1186/1471-2180-11-29",

language = "English",

volume = "11",

journal = "BMC Microbiology",

issn = "1471-2180",

publisher = "BioMed Central Ltd.",

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TY - JOUR

T1 - Enzymatic analysis of the effect of naturally occurring Leu138Pro mutation identified in SHV -lactamase on hydrolysis of penicillin and ampicillin

AU - Rayamajhi, Nabin

AU - Joo, Jeong Chan

AU - Cha, Seung Bin

AU - Pokherl, Subarna

AU - Shin, Min Kyung

AU - Yoo, Young Je

AU - Yoo, Han Sang

N1 - Funding Information: This work was supported by a Korea Research Foundation Grant funded by the Korean Research Foundation (KRF-2006-21-E00011, KRF-2006-005-J502901), a BK-21 grant, and a Bio-green 21 grant (20070401-034-009-007-01-00), RDA and the Research Institute for Veterinary Science, Seoul National University, Korea.

PY - 2011

Y1 - 2011

N2 - Background: The aim of this study was to analyze the significance of leucine to proline substitution at position 138(Leu138Pro) on the hydrolysis of penicillin and ampicillin that we identified in the blaSHVgene of clinical Escherichia coli swine isolate. Results: Kinetic analysis of the mutant proteins showed that Kmvalue of the purified L138P mutant was comparatively higher than SHV-1, SHV-33 and SHV-33(L138P) enzyme for penicillin and ampicillin. Docking simulation of the SHV-1 and SHV-(L138P) enzymes also confirmed that β-lactamases preferred penicillin to ampicillin and the SHV-1 had a higher binding affinity for antibiotics compared to the SHV-(L138P) and other mutants. Conclusions: Our result demonstrated that L138P has a reduced role in penicillin and ampicillin hydrolyzing properties of SHV β-lactamases. These naturally occurring mutations rendering reduced function of the existing protein could trigger the emergence or acquisition of more effective alternative mechanisms for -lactam hydrolysis.

AB - Background: The aim of this study was to analyze the significance of leucine to proline substitution at position 138(Leu138Pro) on the hydrolysis of penicillin and ampicillin that we identified in the blaSHVgene of clinical Escherichia coli swine isolate. Results: Kinetic analysis of the mutant proteins showed that Kmvalue of the purified L138P mutant was comparatively higher than SHV-1, SHV-33 and SHV-33(L138P) enzyme for penicillin and ampicillin. Docking simulation of the SHV-1 and SHV-(L138P) enzymes also confirmed that β-lactamases preferred penicillin to ampicillin and the SHV-1 had a higher binding affinity for antibiotics compared to the SHV-(L138P) and other mutants. Conclusions: Our result demonstrated that L138P has a reduced role in penicillin and ampicillin hydrolyzing properties of SHV β-lactamases. These naturally occurring mutations rendering reduced function of the existing protein could trigger the emergence or acquisition of more effective alternative mechanisms for -lactam hydrolysis.

UR - https://www.scopus.com/pages/publications/79551586439

U2 - 10.1186/1471-2180-11-29

DO - 10.1186/1471-2180-11-29

M3 - Article

C2 - 21291571

AN - SCOPUS:79551586439

SN - 1471-2180

VL - 11

JO - BMC Microbiology

JF - BMC Microbiology

M1 - 29

ER -

Enzymatic analysis of the effect of naturally occurring Leu138Pro mutation identified in SHV -lactamase on hydrolysis of penicillin and ampicillin

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